Targeting of pericytes diminishes neovascularization and lymphangiogenesis in prostate cancer

BACKGROUND. The walls of capillaries in prostate cancer are composed of endothelial cells, and pericytes. NG2 is a transmembrane proteoglycan on nascent pericytes with a functional role in neovascularization. METHODS. The anti-angiogenic effect of hydron pellets containing NG2 neutralizing antibody was quantified in intracorneal PC-3 and LNCaP xenografts. TRAMP and TRAMP-C1 tumors grafted in NG2 knockout mice represented intrinsic pericyte targeting. TRAMP and TRAMP-Cl grafts were analyzed with confocal microscope for microvascular density (MVD) and lymphatic vascular density (LVD). RESULTS. NG2 neutralizing antibody decreased corneal neovascularization in PC3 (P < 0.0001), and LNCaP (P = 0.0079) xenografts. Mean MVD in TRAMP and TRAMP-Cl tumors in NG2 knockout mice were 71% (P = 0.0006) and 63% (P = 0.0011) lower than wild type controls, respectively. Mean LVD in TRAMP and TRAMP-Cl tumors in NG2 knockout mice were 73% (P = 0.0003) and 84% (P < 0.0001) lower than wild type controls, respectively. CONCLUSIONS. Targeting of pericyte-NG2 decreases neovascularization and lymphangio-genesis in prostate cancer significantly.